膝骨关节炎(KOA)不仅与软骨、骨的病变相关，也与肌肉功能和质量的改变相关。肌肉强度、肌肉量、肌肉横截面积、肌肉厚度、肌肉疲劳度等是描述肌肉功能和质量的重要客观量化指标。研究显示，KOA可使肌肉功能和质量发生改变。因此，对于肌肉功能和质量的量化显得尤为重要。本文系统地回顾了临床上肌肉功能和质量的常见指标和测量方法，同时讨论了其与KOA的关系，并整理总结了恢复肌肉功能和质量对KOA患者症状和生活质量改善的意义。

目的 基于系统网络药理学方法探讨当归补血汤治疗骨质疏松(OP)的分子作用机制.方法 通过TCMSP平台筛选当归补血汤主要化学成分、对应靶点及靶标基因,借助GeneCards数据库获取OP已知的相关靶点,将药物靶基因映射到疾病靶基因获得当归补血汤作用于OP的预测靶点;利用Cytoscape 3.5.1软件构建有效活性化合物-疾病靶点网络图以及STRING数据库绘制PPI网络,最后借用R 3.6.3软件进行关键蛋白分析,GO功能分析和KEGG通路富集分析.结果 获得当归补血汤有效活性化学成分共17个,关键成分7个,药物作用于疾病的交集靶点130个,关键靶点30个;GO功能分析揭示当归补血汤治疗OP涉及生物功能主要有核受体活性、配体转录因子活性、调控序列特异性DNA结合、类固醇激素受体活性、细胞因子受体结合、细胞因子活性等;KEGG富集结果显示与糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路、乙型肝炎、前列腺癌、TNF信号通路等密切相关.结论 本研究体现当归补血汤能通过多成分、多靶点、多通路作用于OP,可能与其发挥抗氧化作用和雌激素样作用有关,可为下一步实验验证提供理论基础.

背景:建立标准萎缩性骨不连动物模型是研究萎缩性骨不连的发生机制与治疗的必要条件,而目前常见的造模方法不能准确模拟萎缩性骨不连的临床实际.目的:构建一种新型萎缩性骨不连动物模型.方法:30只雄性SD大鼠随机分成实验组和对照组,均行右侧胫骨中下段截骨,采用环形外固定架固定,维持4 mm缺损间距;其中实验组烧灼截骨端周围1 mm骨膜,对照组不处理骨膜.实验于2018-01-02经广州中医药大学第一附属医院实验动物伦理委员会批准,批号:TCMF1-2018002.结果 与结论:造模后每组分别出现1例外固定架松动,2组均未发生感染;影像学检查显示造模后6周,2组胫骨骨折断端间均无骨性连接,且无进一步愈合迹象;实验组第12周时影像学与组织学显示呈典型萎缩性骨不连表现;对照组第12周影像学显示8只模型呈现肥大性骨不连特征,6只模型影像学具有萎缩性骨不连特征.提示采用环形外固定支架配合烧灼断端骨膜可成功构建萎缩性胫骨骨不连模型.

目的 探讨消炎散中活血化瘀药含药血清对成软骨诱导下兔间充质干细胞(Mesenchymal stem cells,MSCs) Wnt/β-catenin信号通路及SOX9的影响.方法 提取并培养MSCs,先分为成软骨细胞诱导剂组和未成软骨细胞诱导剂组,每组又分为不加血清组、含药血清组、空白血清组、sFRP-3组.采用流式细胞仪检测细胞周期情况,运用RT-PCR、West-ern Blotting检测Wnt信号通路相关Wnt5a、β-catenin,SOX9基因及蛋白水平表达的变化.结果 RT-PCR及WesternBlotting显示,活血化瘀含药血清抑制诱导前MSCs表达Wnt5a、β-catenin mRNA和蛋白,促进SOX9 mRNA和蛋白表达,而对诱导后的MSCs促进WntSa、β-catenin mRNA和蛋白表达,抑制SOX9 mRNA和蛋白表达.结论 消炎散中活血化瘀药含药血清可通过作用Wnt/β3-catenin信号通路,改变SOX9的表达水平,进而影响MSCs的软骨分化.

血管生成与骨生成是促进骨骼生长发育和维持骨量平衡不可或缺的部分,二者之间的耦联作用贯穿骨发育和重塑的整个过程,在新骨生成、骨折愈合、骨缺损修复以及骨质疏松症防治等方面的机制中扮演重要角色.其中血管内皮细胞和血管内皮生长因子等生物活性成分是成血管-成骨耦联中的关键部分,尤其是近些年特异性H型血管的发现丰富了成血管-成骨耦联内容,加深了对二者耦联作用的了解.血管与骨联系密切而又相互作用,血管对于骨骼的意义不仅体现在为骨生长和修复发挥转输氧气、营养物质、生长因子及代谢废物的作用,更为重要的是分泌因子、信号传递、功能调控等方面,而成骨细胞能够分泌或促进分泌血管内皮生长因子等促血管生成因子,对血管生成具有调节作用.故笔者就成血管-成骨耦联相关因子、细胞及机制在骨中所起的作用进行综述.

背景:促进成骨细胞的增殖以及分化是治疗骨质疏松症的有效手段之一,但关于牛膝甾酮对成骨细胞增殖、分化的影响却没有报道.目的:研究牛膝甾酮对SD乳鼠成骨细胞增殖、分化的影响及其潜在的分子机制.方法:通过酶消化法获得SD乳鼠成骨细胞,体外诱导培养并鉴定;采用CCK8法检测不同质量浓度牛膝甾酮(1,5,10 mg/L)对成骨细胞活力的影响;采用碱性磷酸酶染色及碱性磷酸酶活性试剂盒评价成骨细胞的早期分化能力;采用茜素红染色观察钙结节的形成数量,评估成骨细胞的矿化能力;采用实时荧光定量PCR法检测成骨分化标志物的表达水平;采用MDC染色检测自噬小体数量.结果 与结论:①相对于不加药对照组,牛膝甾酮在一定程度上抑制成骨细胞的增殖(P＜0.05),但却能够显著促进碱性磷酸酶活性及矿化结节的形成(P＜0.05),同时上调成骨分化标志物Collagen Ⅰ、OPG、OPN、OCN的表达水平,此外牛膝甾酮还能够促进自噬小体的形成;②结果提示,牛膝甾酮能够通过上调成骨分化相关基因及刺激自噬体的形成而促进成骨细胞的分化.

背景:引导骨再生技术作为目前应用最广泛的骨缺损修复方法之一已广泛运用于口腔医学领域,但关于引导骨再生技术在长骨骨干骨缺损中应用的研究报道很少.目的:探究引导骨再生技术结合中药补肾治疗对大鼠股骨骨缺损修复的影响,评估其成骨效能,并探讨其作用机制.方法:将36只SD大鼠随机分为6组(n=6):空白组、引导骨再生组、补肾高剂量组、补肾中剂量组、补肾低剂量组、骨肽片(西药)组,建立大鼠股骨骨缺损模型,除空白组外,其余各组均给予引导骨再生治疗,采用引导骨再生技术植入自体骨及Bio-Gide胶原膜;补肾各剂量组分别给予0.216,0.108,0.054 g/(kg·d)的强骨胶囊灌胃治疗8周;骨肽片组予以0.58 mg/(kg·d)骨肽片灌胃治疗8周.术后第12周,以X射线检查、骨组织苏木精-伊红染色及Masson染色为主要评价指标,评估成骨情况;采用实时荧光定量RT-PCR法检测骨组织中碱性磷酸酶、核心结合因子2、血管内皮生长因子及骨形态发生蛋白2 mRNA的表达.结果 与结论:①X射线检查、骨组织苏木精-伊红染色及Masson染色结果显示,各治疗组Lane-Sandhu X射线评分与Huddleston组织学评分均显著高于空白组(P＜0.001),其中补肾高剂量组和补肾中剂量组明显高于引导骨再生组(P＜0.01);②RT-PCR检测结果显示,与空白组相比较,补肾高剂量组和补肾中剂量组对骨组织中碱性磷酸酶、核心结合因子2、血管内皮生长因子及骨形态发生蛋白2 mRNA的表达有显著上调作用(P＜0.01),且明显优于引导骨再生组(P＜ 0.05);③提示引导骨再生技术结合中药补肾法治疗能明显促进大鼠股骨骨缺损修复、减少骨组织吸收并改善成骨效能.其作用机制可能是在膜屏障创造出骨组织优势生长的环境中,通过上调相关成骨因子及血管生成因子的表达,促进骨组织新生及血管形成.

背景:目前国内外学者试图通过改变植入材料的种类和形貌、改良诱导膜厚度、光滑程度等机械化学性能来促进植骨生长。目的:比较大鼠股骨骨缺损处不同表面粗糙程度聚甲基丙烯酸甲酯骨水泥形成的诱导膜在膜内血管化程度和部分成骨因子表达的差异。方法:取48只雄性SD大鼠（购自广州中医药大学实验动物中心）建立大鼠临界尺寸股骨缺损模型,按随机数字表法分为A、B、C、D组,分别在股骨骨缺损处植入表面粗糙度＜1.5μm、1.5-2.0μm、5.0-7.0μm、14.0-20.0μm的聚甲基丙烯酸甲酯骨水泥占位器。植入6周大鼠体内诱导膜形成后取出骨水泥周围的诱导膜,苏木精-伊红染色观察诱导膜病理组织形态结构变化,采用Western Blot印迹方法和免疫组织化学染色法对诱导膜中骨形态发生蛋白2、转化生长因子β1、血管内皮生长因子蛋白进行定量和定性分析。实验获得广州中医药大学动物实验伦理委员会批准,批准号:20181101006。结果与结论:①苏木精-伊红染色显示,4种表面粗糙程度不同的骨水泥均可以形成较为规则的诱导膜,4组诱导膜之间血管化程度和细胞的数量大体相似;②Western Blot印迹检测显示,各组诱导膜内骨形态发生蛋2、转化生长因子β1、血管内皮生长因子蛋白平均含量基本相似（P＞0.05）;③免疫组织化学染色显示,各组诱导膜内骨形态发生蛋2、转化生长因子β1、血管内皮生长因子蛋白阳性表达基本相似（P＞ 0.05）;④结果表明,骨水泥表面粗糙程度改变对诱导膜的组织形态结构和骨形态发生蛋2、转化生长因子β1、血管内皮生长因子表达在6周时无明显影响。

Objective:To evaluate the efficacy and safety of Shenmai Injection in treating knee osteoarthritis by Meta-analysis.Methods:Databases including China National Knowledge Infrastructure (CNKI), WanFang Data, Weipu China Soience and Technology Journal Databases (VIP database), Chinese Biomedical Databases (CBM), PubMed, Embase and Cocbrane Library were searched to collect data of randomized controlled trials (RCTs) with respect to Shenmai Injection for knee osteoarthritis (KOA) according to Cochrane systematic review, and data analyses were performed by Revman 5.3 software and grading of evidence quality were assessed with the GRADE system.Results:A total of 15 RCTs involving 1228 cases were identified, with 619 patients in treatment group and 609 patients in control group. Meta-analysis indicated that no statistically significant differences were found in both treatment and control groups regarding to total effcacious rate, Lequesne index, Visual Analogue Scale (VAS) score and adverse reactions (P>0.05).However, the number of adverse reactions in treatment group was gerater than that in control group. There were statistical differences in WOMAC scale[MD=-9.55, 95％CI (-13.17,-5.94), P<0.000 01], Lysholms score[MD=5.41, 95％CI (3.52, 7.30), P<0.000 01], AKS score (P<0.000 01) and good rate[OR=2.22, 95％CI (1.11, 4.43), P=0.02]. The GRADE evaluation of the evidence quality showed the evidence of quality was low.Conclusion:Shenmai Injection is effective in treating KOA. Both groups show equivalent effects on total effcacious rate, Lequesne index and VAS score, whereas Shenmai Injection has better efficacies in WOMAC scale, Lysholms score, AKS score and good rate. However, certain adverse events may occur and more attentiom should be paid to in clinic.

目的:观察通络止痛外敷散联合唑来膦酸治疗不同部位骨转移癌疼痛患者的疗效.方法:将60例骨转移癌患者随机分为治疗组和对照组,各30例,对照组予唑来膦酸静脉滴注,治疗组予唑来膦酸静脉滴注联合通络止痛外敷散超微颗粒外敷,治疗3个月后评估两组治疗效果治疗前后NRS评分、KPS生活质量评分变化情况及毒副反应情况.结果:与对照组比较,治疗组患者在改善NRS评分、KPS生活质量评分方面疗效更优(P＜0.05);在降低血清ALP水平方面也优于对照组患者(P＜0.05).结论:通络止痛外敷散联合唑来膦酸可以改善癌痛患者的疼痛,提高癌痛患者的生活质量.

Objective: In this study, we collected the prescriptions of professor HUANG Feng used for the out-patients with knee osteoarthritis and analyzed the composing principles of the prescriptions by using traditional Chinese medicine (TCM) inheritance support platform (V2.5). Methods: We collected the prescriptions used for KOA cases, then the data was entered into the TCM inheritance support platform and analyzed based on principle analysis, revised mutual information, complex system entropy cluster and unsupervised hierarchical clustering composing principles. Results: Based on the analysis of prescriptions of 429 cases, the frequency of each Chinese medicinal herb and association rules among herbs included in the database were computed and 6 new prescriptions were explored from the database. Conclusion: The methods of replenishing Qi, invigorating spleen, dispelling dampness and promoting Qi and activating blood to arrest pain were the key processes of professor HUANG Feng in treating KOA, assisted by herbal medicines of invigorating the kidney and strong bone, relaxing tendons and activating collaterals and nourishing Yin, which suggests the diagnosis and treatment of KOA starting from the spleen and kidney, taking into account the congenital and acquired foundation and principles of emphasis on both sinews and bones.

目的:探讨骨碎补总黄酮对大鼠Masquelet诱导膜血管新生因子表达的影响.方法:选取SPF级雄性SD大鼠60只,按体质量分层后随机分为空白组、模型组、中药低剂量组、中药中剂量组、中药高剂量组5组,每组12只.建立大鼠股骨诱导膜模型后,于造模后第2天开始用不同浓度的骨碎补总黄酮给各中药组灌胃,模型组及空白组给予等量纯水灌胃,直至造模后第28天.采用Western Blot、免疫组化及Q-PCR分别检测各组诱导膜组织中血管新生相关因子:VEGF、HMGB1、PDGF-BB、CD31、Emcn蛋白和基因的表达.结果:免疫组化显示诱导膜组织中CD31蛋白为强阳性表达,而Emcn的表达为弱阳性.模型组较空白组各血管新生因子mRNA及蛋白表达明显提高(P＜0.05);中药高剂量组中二者的表达较模型组一致上调(P＜0.05).结论:虽诱导膜中不存在CD31hiEmcnhi血管,但骨碎补总黄酮对诱导膜中血管新生相关因子表达有明显的上调作用.

目的:观察两种补肾法在牵张成骨(DO)中对血管生成及新骨生成的影响,评估成骨效能,并对作用机制进行探讨.方法:50只SD大鼠随机分为5组:补肾阳组、补肾阴组、西药组、模型组和空白组,每组10只.构建胫骨DO模型,给予补肾阳法和补肾阴法干预,4周和8周后分别行X线、HE和Masson染色评估成骨情况,血管造影观察牵张区血管形成,ELISA检测骨髓中VEGF、Ang-2、Runx-2和BMP-2含量水平,qPCR检测骨中对应因子的mRNA表达.结果:X线、HE和Masson染色示补肾阳组和补肾阴组的成骨效果明显优于对照组与模型组,两种补肾法均可提高Lane-Sandhu、Huddleston分值(P＜0.05).与对照组与模型组比较,补肾阳、补肾阴两组可显著增加血管体积分数(P＜0.05),上调VEGF、Ang-2和Runx-2、BMP-2及相应mRNA的表达(P＜0.05),其中补肾阳组VEGF、Ang-2及其mRNA表达最高,而补肾阴组Runx-2、BMP-2及其mRNA表达最高.结论:补肾阳法和补肾阴法均可上调DO中成血管-成骨因子表达,促进血管生成和新骨形成,从而改善成骨效能、促进骨修复,但二者的作用机制存在差异.

目的:探讨骨碎补总黄酮在诱导膜技术(Masquelet)技术中对骨缺损区域血管形成和成骨质量的影响.方法:36只雄性SD大鼠分为3组(空白组、诱导膜组、诱导膜+中药组),每组12只,右侧股骨截骨4mm,均采用钢板固定,置入PMMA骨水泥旷置4周,空白组不予植骨,诱导膜组及诱导膜+中药组旷置后行尾骨植骨术,术后通过大体观察、影像学观察以及组织形态学方法观察截骨部位的愈合与血管形成情况.结果:诱导膜+中药组在血管形成、骨质矿化、骨质塑性、组织形态学方面均优于其他两组.结论:骨碎补总黄酮在Masquelet技术中对骨缺损区域的成骨质量和血管形成具有良好的促进作用.

Wnt/Ca2+信号通路属于Wnt非经典通路,该通路的失调与细胞调亡、炎症反应等病理改变,以及许多疾病的发生、发展、转归有着密切联系.肢体缺血/再灌注损伤(LIRI)是临床工作中常遇到的一类难题,而Wnt/Ca2+通路可诱使细胞内Ca2+浓度升高并可活化Ca2+敏感信号成分,其介导的细胞凋亡、Ca2+超载和机体炎症等反应在LIRI中扮演重要角色.该文就Wnt/Ca2+信号通路在LIRI病机中所起的作用进行综述.

Objective:To observe Yutan capsule on functional recovery of spinal cord after angioplasty of open-door laminoplasty spinal canal multi segmental cervical spondylotic myelopathy.Methods:81 cases of patients with cervical spondylotic myelopathy according to the methods of treatment were divided into A group (surgery + o-ral Yutan capsule) and B group (surgery + oral Methylcobalamin dispersible tablets).After 13-25 months of fol-low-up,all patients with preoperative and postoperative 1d,6months,1 years after surgery for cervical JOA score and comparative analysis.Results:1 day after operation,two groups of JOA score compared with preoperative changed obviously (P<0.05);6 months after operation,two groups no significant difference (P<0.05);1 year after opera-tion,group a JOA score was better than that of group B,the difference was statistically significant (P<0.05);effi-cacy rate was 93.18％ 1 year after operation in group A,group B effectiveness 83.78％,the difference was statistical-ly significant (P<0.05).Conclusion:Yutan Capsule on cervical spondylotic myelopathy,laminoplasty after recovery of spinal cord function has a positive effect,is worthy of promotion.

目的:观察桃红四物液对肢体缺血-再灌注损伤大鼠骨骼肌细胞凋亡的影响.方法:2月龄雄性SD大鼠50只,按随机数字表法分为5组:正常组、缺血再灌注组(IR组)、桃红四物液低剂量组(TD-IR组)、桃红四物液中剂量组(TZ-IR组)和桃红四物液高剂量组(TG-IR组),每组10只.复制肢体缺血再灌注损伤模型,采用HE染色法观察骨骼肌细胞形态学变化,DAPI法检测细胞凋亡.结果:①除正常组外,各组均出现不同程度肌纤维肿胀、排列不规则、肌纤维间隙增宽等情况,较之IR、TG-IR两组,TD-IR、TZ-IR两组损伤较轻,TG-IR组损伤程度最重.②IR、TG-IR、TD-IR和TZ-IR 4组骨骼肌细胞凋亡率降较正常组升高(P＜0.05),与IR、TG-IR两组比较,TD-IR、TZ-IR两组细胞凋亡率降低(P＜0.05),且TZ-IR组最低、TG-IR组最高.结论:一定剂量的桃红四物液能减轻肢体缺血-再灌注损伤,降低损伤骨骼肌细胞的凋亡率,对骨骼肌有一定的保护作用,本实验中中剂量桃红四物液效果最佳,高剂量的桃红四物液反可加重肢体缺血再灌注损伤,因此在临床上应严格控制好用药剂量.

目的 介绍一种改良的体外闭合阻断股动脉血流的方法,建立简便可控、质量可靠的肢体缺血-再灌注损伤(limb ischemia-reperfusion injury,LIRI)大鼠模型.方法 15只2月龄SPF级SD雄性大鼠随机分为5个组:正常组,缺血再灌注0 h组、2 h组、4 h组和8 h组.正常组不阻断血流,其余4组构建缺血-再灌注损伤模型,采用HE染色法观察骨骼肌细胞形态学变化,DAPI法检测细胞凋亡.结果 除正常组外,各组均出现不同程度肌纤维肿胀、排列不规则、肌纤维间隙增宽等情况,4 h和8 h两组损伤程度较之0 h和2 h两组显著加重,8 h组损伤程度最重,且四组骨骼肌细胞表现出典型的凋亡形态学特征.结论 此方法能反映LIRI过程中骨骼肌的病理变化特点,与LIRI临床特征相似,操作简便、高效,可用于肢体缺血-再灌注动物模型的构建.

Objective:To observe the effect of Taohong Siwu Liquid on rats with LIRI and explore the mechanism.Methods:A total of 102 male rats were randomly divided into 5 groups:control group,group IR,group TD-IR (low Taohong Siwu Liquid),group TZ-IR(middle Taohong Siwu Liquid) and group TG-IR(high Taohong Siwu Liquid) and except control group,they were divided into 0 h,2 h,4 h and 8 h groups.After establishing limb ischemia reperfusion injure model,the volumons and gene expressions of TNF-o and IL-1 β were detected by ELISA and RT-PCR.Results:①Compared with control group,the levels of TNF-α and IL-1β were significantly higher (P ＜ 0.05) and TD-IR group and TZ-IR group's TNF-α and IL-1 β at the same time point were lower than those of the IR group,but TG-1R group's was higher (P ＜ 0.05).②Compared with control group,the mRNA levels of TNF-α and IL-1 β in skeletal muscle of the other four groups were higher (P ＜ 0.05) and TD-IR and TZ-IR were lower than those of the IR group whereas TG-IR were higher than those of the IR group.③At the time point of 2 h,the volume of TNF-α and IL-1 β were the highest.Conclusions:①The expressions of TNF-α and IL-1β in the serum and skeletal muscle of rats with ischemia-reperfusion injury increased.②At the time point of 2h,TNF-α and IL-1 β reached the peak,and maintained at a high level during 2h to 8h period,and the reperfusion injury gradually deteriotered.③A certain dose of Taohong Siwu Liquid could reduce the damage of LIRI and the apoptosis and had positive effects on the skeletal muscle and in this study,the medium dose of Taohong Siwu Liquid had the best treatment effect,but the high dose could aggravate damages of LIRI.

Wnt/Ca2+信号通路属于Wnt非经典通路，该通路的失调与细胞调亡、炎症反应等病理改变，以及许多疾病的发生、发展、转归有着密切联系。肢体缺血/再灌注损伤(LIRI)是临床工作中常遇到的一类难题，而Wnt/Ca2+通路可诱使细胞内Ca2+浓度升高并可活化Ca2+敏感信号成分，其介导的细胞凋亡、Ca2+超载和机体炎症等反应在LIRI中扮演重要角色。该文就Wnt/Ca2+信号通路在LIRI病机中所起的作用进行综述。